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PubMed1999

Epithelial-myoepithelial carcinoma arising in the nasal cavity: a case report and review of literature.

Epithelial-myoepithelial carcinoma is an uncommon, low-grade, malignant epithelial neoplasm composed of variable proportions of ductular cells and large, clear staining, myoepithelial cells arranged around the periphery of the ducts. About 120 cases have been reported in the world literature, most of which were located in salivary glands, except for a few cases occurring in unusual locations such as breast, lacrimal gland, nose, paranasal sinus, trachea, bronchus, and lung. We here reported the second case of epithelial-myoepithelial carcinoma of the nasal cavity with extension to the nasopharynx. The patient was a 61 year old Chinese female with two month's history of progressive nasal obstruction. Histopathologically, the tumor showed typical myoepithelial and ductal cells biphasic differentiation, duct-like structure and infiltrating growth pattern. Some ductal cells showed the characteristics of oxyphilic cell, which had never been reported before. Recurrence and metastasis rates of epithelial-myoepithelial carcinoma varied from 35% to 50% and 8.1% to 25% respectively in different reports. The present case had neither recurrence nor metastasis twenty months after operation. When epithelial-myoepithelial carcinoma is mainly composed of spindle myoepithelial cells, the differential diagnosis should include myoepithelioma, neurofibroma, leiomyoma and hemangiopericytoma.

Biomarkers, Tumor↗

PubMed2006

Prognostic significance of homozygous deletions and multiple duplications at the CDKN2A (p16INK4a)/ARF (p14ARF) locus in urinary bladder cancer.

OBJECTIVE: The 9p21 locus is a major target in the pathogenesis of human urinary bladder cancer. This locus harbours the CDKN2A/ARF tumour suppressor gene, which encodes two cell-cycle regulatory proteins: p16INK4a and p14ARF. We studied how homozygous deletions and multiple duplications at this locus affect prognosis and survival in patients with bladder cancer. MATERIAL AND METHODS: Real-time quantitative polymerase chain reaction (QPCR), based on simultaneous amplification of ARF and a reference gene, glyceraldehyde-3-phosphate dehydrogenase, was used to measure homozygous deletions and multiple duplications in a population-based material consisting of 478 patients with urinary bladder cancer. Results from real-time QPCR were compared with clinico-pathological parameters and survival curves were generated using the Kaplan-Meier method. RESULTS: Real-time QPCR analysis showed 71 (15%) homozygous deletions and 8 (2%) multiple duplications. We were unable to find any association between either stage or grade and urinary neoplasms with homozygous deletions. However, although there were only a limited number of patients with multiple duplications, 7/8 of them had highly malignant tumours (G2b-G4 or > or = T1; p = 0.02). CONCLUSIONS: Urinary bladder cancers constitute a spectrum of neoplasms with varying clinical manifestations. We were unable to establish a prognostic relevance for patients with tumours harbouring homozygous deletions at the CDKN2A/ARF locus. However, our data did indicate that patients with multiple duplications at the CDKN2A/ARF locus had poor survival. This suggests that multiple duplications, in combination with other genetic changes, have cooperative effects which have a negative outcome on urinary bladder cancer prognosis.

Carcinoma, Transitional Cell↗

PubMed1995

Adjuvant treatment for early epithelial ovarian cancer: results of two randomised clinical trials comparing cisplatin to no further treatment or chromic phosphate (32P). G.I.C.O.G.: Gruppo Interregionale Collaborativo in Ginecologia Oncologica.

BACKGROUND: From 1983 to 1990, 271 consecutive patients with stage I ovarian cancer entered two randomised trials, aimed at assessing the role of adjuvant chemotherapy after radical surgery in early stages of ovarian cancer. Trial I compared cisplatin (50 mg/m2 with repeated courses every 28 days for 6 cycles) to no further therapy in F.I.G.O. stage Ia & b Grade II-III patients; trial II compared cisplatin (same dose and schedule) to 32P in Iaii & bii and Ic patients. METHODS: Both studies were multicentric and centrally randomized. Treatment was allocated by phone and stratified by center. All patients satisfying major eligibility criteria (histological and grade, no previous neoplasms) were analysed according to treatment allocated by randomisation. RESULTS: With a median observation time of 76 months, cisplatin significantly reduced the relapse rate by 65% (HR = 0.35; 95% CI = 0.14-0.89, p = 0.028; Cox Model) in trial I and 61% (HR = 0.39; 95% CI = 0.19-0.77, p = 0.007; Cox Model) in trial II. Survival was not significantly different (trial I - Kaplan-Meier overall 5-year survival: cisplatin = 88%, control = 82%, HR = 1.15; 95% CI = 0.44-2.98; p = 0.773; Cox Model); trial II - overall 5-year survival: cisplatin = 81%, 32P = 79%, HR = 0.72; 95% CI = 0.37-1.43; p = 0.354; Cox model). In both studies the risk of dying after relapse increased for patients originally randomized to the cisplatin arms: in trial I, 6 of 7 patients in the cisplatin relapsed arm and died of tumor compared with 8 of 14 patients in the control arm. In trial II 11 of 12 patients on cisplatin, and 18 of 26 on 32P succumbed to tumor recurrence. CONCLUSION: Adjuvant cisplatin treatment in early ovarian cancer significantly prevents relapse in comparison to 32P in stage IC patients or to no immediate treatment in earlier stage women. The impact of cisplatin adjuvant treatment on survival remains, however, unclear.

Adult↗

PubMed2000

Intraepidermal Merkel cell carcinoma with no dermal involvement.

Cutaneous Merkel cell carcinoma (MCC) typically involves the dermis. Less than 10% of MCC have epidermal involvement. Only one MCC confined exclusively to the epidermis has been previously reported but was not recognized until the lesion recurred with typical MCC in the dermis. We present a case of a wholly intraepidermal pagetoid MCC without dermal involvement in a 74-year-old man with a 2.0-cm solitary verrucous papule on the left index finger. The initial biopsy and complete excision specimens showed marked epidermal hyperplasia, focal prominent squamous cell atypia, and MCC with florid pagetoid spread through the epidermis. There was no evidence of tumor within the dermis. The pagetoid MCC tumor cells showed diffuse cytoplasmic staining with antibodies to cytokeratin 20, and negative staining for chromogranin, neurofilament, S-100, vimentin, HMB45, leukocyte common antigen, and CD3. The cell of origin of MCC is still debated. The existence of an entirely intraepidermal variant of MCC would lend support to the view that MCC is a neoplastic expression of Merkel cells in at least some cases. Dermal-based MCC is a high-grade primary cutaneous neoplasm, but MCC confined exclusively to the epidermis may have a better prognosis.

Aged↗

PubMed1991

Ploidy analysis and S-phase fraction determination by flow cytometry of invasive adenocarcinomas of the breast.

The results of flow cytometric analysis of ploidy and S-phase fraction for invasive breast cancers have been compared with various clinical and pathologic parameters by many investigators. Ploidy usually has been found to be associated with histologic type, tumor grade, and S-phase fraction values, but not with patient age, menopausal status, tumor size, axillary nodal status, estrogen receptor status, or progesterone receptor status. S-phase fraction values have correlated with histologic type, grade, estrogen receptor status, and progesterone receptor status, but not with menopausal status or axillary nodal status. Although in several studies ploidy and S-phase fraction have been compared with patient outcome, only a few of these reports have stratified data according to the histologic types and grades of the neoplasms. There is conflicting information regarding the value of ploidy analysis for women with either node-negative or node-positive breast carcinoma. Data from a few studies seem to indicate that S-phase fraction alone or in combination with ploidy may be more important prognostically than ploidy alone, although the results have not been uniform. More studies that examine ploidy, S-phase fraction, various important clinical and pathologic variables, and outcome for patients with invasive mammary cancer must be performed before the clinical importance of DNA analysis by flow cytometry becomes known.

Adenocarcinoma↗

PubMed1999

Congenital disseminated malignant rhabdoid tumor: a distinct clinicopathologic entity demonstrating abnormalities of chromosome 22q11.

The clinical, pathologic, and immunohistochemical features of a widely disseminated tumor with rhabdoid phenotype are described in nine infants < or = 3 months of age. Five neonates had tumor evident at birth, two of which had placental metastases. The average survival following diagnosis was < 6 weeks. None of the infants had an apparent primary tumor in either the kidney or brain. In four cases, the dominant mass involved the head and neck region, and in two cases, the primary mass was paraspinal. The histologic features were those of a high-grade, round cell neoplasm with abundant cytoplasm and containing cells with cytoplasmic filamentous inclusions. Immunohistochemical studies revealed polyphenotypic antigen expression. Genetic information was available from eight of nine cases. Karyotype analysis revealed abnormalities of chromosome band 22q11-12 in three of six tumors. Fluorescence in situ hybridization studies or molecular studies demonstrated 22q11.2 deletions in all five cases with available frozen tissue, two of which had translocations involving 22q by karyotype analysis. The similar clinical and pathologic findings in these rapidly fatal tumors in infants and the demonstration of abnormalities of chromosome 22q11 in a majority of the cases supports their histogenetic and nosologic relationship to the family of malignant rhabdoid tumors that typically occur in young children in several anatomic sites, including kidney, soft tissues, liver, and brain. Like neuroblastoma and rhabdomyosarcoma, malignant rhabdoid tumor can appear as disseminated disease at birth or shortly thereafter.

Chromosomes, Human, Pair 22↗

PubMedDate not supplied

MR imaging of spindle cell hemangioendothelioma.

Spindle cell hemangioendothelioma is a slowly progressing vascular tumor of low grade malignancy. This neoplasm has been reported in 33 patients but in only one patient were osseous lesions seen. The only other description regarding imaging of this tumor was CT demonstrating soft tissue masses in the thigh without osseous involvement. We present a case of spindle cell hemangioendothelioma in which magnetic resonance further defined the radiographic features of this newly recognized tumor.

Adolescent↗

PubMed1997

Human telomerase RNA expression and MIB-1 (Ki-67) proliferation index distinguish hemangioblastomas from metastatic renal cell carcinomas.

Hemangioblastomas are low-grade, capillary rich neoplasms of the cerebellum and spinal cord that can occur sporadically or in the setting of Von Hippel-Lindau syndrome. The present study analyzed the utility of proliferation potential in differentiating hemangioblastoma from RCC metastatic to the central nervous system using a MIB-1 (Ki-67) labeling index and assessment of expression of the RNA component of telomerase. Immunohistochemical analysis for epithelial membrane antigen (EMA) and MIB-1 was performed on paraffin-embedded sections of 27 hemangioblastomas and 5 RCC metastatic to the central nervous system. All but one hemangioblastoma demonstrated low or negative MIB-1 immunoreactivity, while 4 of 5 RCC metastases had moderate or high labeling indices. Telomerase RNA expression was assessed in 10 hemangioblastomas and in all 5 metastatic RCC by in Situ hybridization. All 10 hemangioblastomas demonstrated a lack of expression of telomerase RNA, while all 5 metastatic RCCs showed moderate to strong expression. Our results suggest that the MIB-1 labeling index is useful in differentiating hemangioblastoma from metastatic RCC and assessment of telomerase expression can also provide novel information on the difference in growth potential of these tumors.

Adolescent↗

PubMed1988

Epithelial tumors of the ovary in women less than 40 years old.

From Jan 1, 1978 through Dec 31, 1983, 64 patients with epithelial ovarian tumors, frankly malignant or borderline, were managed at one institution. Nineteen patients (29.7%) were under age 40. The youngest patient was 19 years old. Nulliparity was present in 32% of this group of patients. Of these young patients, 58% had borderline epithelial tumors, compared to 13% of patients over 40 years of age. Twenty-one percent of the young patients were initially managed by unilateral adnexal surgery. The overall cumulative actuarial survival rate of all young patients was 93%. Young patients with epithelial ovarian tumors tend to have earlier grades of epithelial neoplasms, and survival is better than that reported for older patients with similar tumors.

Adult↗

PubMed2004

An allograft model of androgen independent prostatic neuroendocrine carcinoma derived from a large probasin promoter-T antigen transgenic mouse line.

PURPOSE: Animal models that mimic this hormone refractory prostate cancer may be useful for developing and testing novel treatment strategies. MATERIALS AND METHODS: Using the prostate of the 12T-10 transgenic mouse an allograft model was established by transplantation into a nude mouse. To our knowledge we describe the first allograft model derived from the primary prostate tumor of a transgenic mouse. RESULTS: The primary tumor progressed from high grade prostatic intraepithelial neoplasm to invasive, undifferentiated and metastatic cancer with loss of androgen receptor expression. After 10 passages in nude mice the allograft retained the same histological and immunohistochemical features as the primary tumors, including neuroendocrine differentiation. The allograft demonstrated androgen independent growth and metastases to liver and lung, paralleling tumor behavior in the original transgenic line. Cytogenetic characterization of the allograft revealed consistent chromosomal abnormalities for multiple in vivo passages. CONCLUSIONS: This allograft model may give insight into the mechanism by which human prostate cancer progresses to an androgen independent state and provide a system for testing drugs that can inhibit this disease.

Androgen-Binding Protein↗

PubMed2006

CDX-2 expression in pseudomyxoma peritonei: a clinicopathological study of 42 cases.

AIMS: CDX-2 is a highly sensitive and specific marker of intestinal epithelial cells and their neoplastic counterparts. CDX-2 status in pseudomyxoma peritonei (PMP) has been barely reported. The aim of this study was to investigate the clinicopathological features of 42 cases of PMP with a special emphasis on CDX-2. METHODS AND RESULTS: All patients were treated by cytoreduction. Immunohistochemistry was performed for CDX-2, MUC-2, MUC-5AC, cytokeratin (CK) 7 and CK20. Statistical correlation was evaluated for age, sex, completeness of cytoreduction and histological subtype with overall and progression-free survival (OS and PFS). PMP consisted of 32 cases of disseminated peritoneal adenomucinosis and 10 cases of peritoneal mucinous carcinomatosis. The appendix evaluated in 25 cases showed two mucinous adenocarcinomas and 21 low-grade appendiceal mucinous neoplasms. CDX-2 was diffusely positive in 40 cases, with the remaining two cases being focally positive. All cases demonstrated diffuse reactions to CK20 and MUC-2, and variable reactions to MUC-5AC, while CK7 was variably positive in 38 cases. Five-year OS was 97%. Histological type was significantly correlated with PFS (P=0.02). CONCLUSIONS: CDX-2 is diffusely and strongly positive in PMP. This is a useful marker to confirm an appendiceal origin of PMP, particularly when used in conjunction with CK7, CK20, MUC-2 and MUC-5AC.

Adult↗

PubMed1998

Histopathologic and flow-cytometric analysis of neoplastic and benign "background" tissue in breast carcinoma resections.

Two-color, multiparametric synthesis phase fraction (SPF) analysis of cytokeratin-labeled epithelial cells was flow cytometrically performed on both benign (SPFb) and malignant tissue samples (if available, SPFt) from 132 mastectomy/lumpectomy specimens. These data were then correlated with clinicopathologic features, including (1) tumor differentiation, (2) the proportion of tumor comprised of duct carcinoma-in situ (DCIS), and (3) the histology of accompanying benign breast tissue, classified by predominant microscopic pattern as intact, normal terminal duct lobular units (NTDLU, 34% of cases), atrophic (AT, 33% of cases), proliferative fibrocystic (PFC, 26% of cases), and non-proliferative fibrocystic (NPFC, 7% of cases). SPFt was inversely correlated with extent of DCIS (DCIS = 0-20% tumor volume - 12.7% mean SPFt, vs. DCIS >20% tumor volume - 6.4% mean SPFt, p = 0.001). SPFt also correlated with the histology of background benign breast tissue (NTDLU - 14.8% mean SPFt vs. AT - 6.9% mean SPFt vs. PFC - 12.7% mean SPFt, p = 0.05) but it did not correlate with patient age or SPFb (overall mean = 0.73%). SPFb was correlated with patient age (>56 yr - 0.59% mean SPFb vs. <56 yr - 0.84% mean SPFb, p = 0.02), with background histology (NTDLU - 1.1% mean SPFb vs. AT - 0.43% mean SPFb vs. PFC - 0.70% mean SPFb, p < 0.02) and with the grade of the neoplasm (well/moderate - 0.58% mean vs. poorly differentiated - 0.85% mean, p = 0.04). Patients having a background of PFC were significantly older than patients with a background of NTDLU (45.2 yr vs. 60.2 yr, p = 0.01). We conclude: (1) breast carcinomas arising from a background of more actively cycling pre-involutional or proliferative fibrocystic epithelium have a greater proliferative fraction than tumors arising from atrophic epithelium, implying that the differentiation status of target cells may impact the effect(s) of tumorigenic events; (2) PFC may represent delayed, abnormal or interrupted involution rather than a hyperproliferative state relative to NTDLU, suggesting that it facilitates neoplasia by extending the period of exposure to promoter agents such as endogenous hormones, and (3) lower SPFt in breast neoplasia with more abundant "residual" DCIS may reflect a lengthier pre-invasive disease interval due to intrinsically less aggressive phenotype.

Breast↗

PubMed2006

A novel somatic mouse model to survey tumorigenic potential applied to the Hedgehog pathway.

We report a novel mouse model for the generation of sporadic tumors and show the efficiency of this approach by surveying Hedgehog (Hh)-related tumors. Up-regulation of the Hh pathway is achieved by conditionally regulated expression of an activated allele of Smoothened (R26-SmoM2) using either sporadic leakage or global postnatal induction of a ubiquitously expressed inducible Cre transgene (CAGGS-CreER). Following postnatal tamoxifen induction, CAGGS-CreER; R26-SmoM2 mice developed tumors with short latency and high penetrance. All mice exhibited rhabdomyosarcoma and basal cell carcinoma; 40% also developed medulloblastoma. In addition, mice showed a novel pancreatic lesion resembling low-grade mucinous cystic neoplasms in humans. In contrast, widespread activation of SmoM2 in the postnatal prostate epithelium results in no detectable morphologic outcome in 12-month-old mice. Comparison of gene expression profiles among diverse tumors identified several signature genes, including components of platelet-derived growth factor and insulin-like growth factor pathways, which may provide a common mechanistic link to the Hh-related malignancies. This experimental model provides a robust tool for exploring the process of Hh-dependent tumorigenesis and the treatment of such tumors. More generally, this approach provides a genetic platform for identifying tumorigenic potential in putative oncogenes and tumor suppressors and for more effective modeling of sporadic cancers in mice.

Alleles↗

PubMed2000

Malignant cylindroma in Brooke-Spiegler syndrome.

A 68-year-old female patient presented with a history of gradual appearance of multiple nodules situated predominantly on the scalp and neck, with a few nodules on the trunk. The nodules began to appear at the age of 30. Family history revealed that the patient's brother, son, father and grandmother had similar cutaneous lesions. The dominant histopathological pattern was that of a cylindroma. Features of both cylindroma and spiradenoma (spiradenocylindroma) were present within the same lesion in some biopsies. Most lesions on the scalp were skin-colored with a smooth surface. The largest tumors located on the neck were tender and ulcerated. Histopathologically, these tumors had the morphology of a high-grade malignant solid neoplasm with epithelioid features.

Aged↗

PubMed2000

Expression of wild-type p53 and Bcl-2 family genes oscillates with recurrent remission and relapse in an unusual case of low-grade lymphoma.

Downregulation of apoptosis has been proposed as a mechanism of clonal expansion in low-grade B cell neoplasms. We have previously described an unusual case of CD5+ B cell lymphoma characterized by cycles of leukemic phase alternating with spontaneous remission. In the present study, we examined the involvement of apoptosis-related proteins in the progression of this cyclic lymphoma ex vivo. During the leukemic phases, the clonal cells were activated blasts expressing elevated levels of wild-type (wt) p53, Bcl-2, Bcl-x(L), and Bax, while Bak expression increased during the decline of lymphocytosis. Bax heterodimerized with Bcl-2 but not with Bcl-x(L). The anti-apoptotic Bcl-2/Bax heterodimers peaked during early leukemic phases and declined during regression. The elevation in Bcl-2, Bcl-x(L) and Bax expression during early leukemic phases seems to result from cell activation since a similar increase was induced by activating the remission phase leukemic cells in culture. The data suggest that wt p53, Bcl-x(L), and Bcl-2/Bax heterodimers support the accumulation of activated leukemic cells during the leukemic phases, while Bax and Bak may be involved in their decline during regression.

Acute Disease↗

PubMed1982

Are the histological and ultrastructural features of endometrial carcinomas reliable indicators of their steroid receptor content?

The histological and ultrastructural features of 15 endometrial carcinomas were analyzed and recorded without knowledge of the steroid receptor content which was determined in the cytosol of the tumor tissue. Serum levels of estrogens were determined in all patients. The importance of this simultaneous determination of the levels of circulating steroid hormones is emphasized. Some degree of correlation was found between the histological grading of the neoplasms and their steroid receptor content. On the contrary, no evident relation seems to exist between steroid hormone-binding capacity and ultrastructural features of the tumor cells. These different results are presented and discussed.

Aged↗

PubMedDate not supplied

Fine needle aspiration biopsy of well-differentiated liposarcoma of the neck in a young female. A case report.

BACKGROUND: Well-differentiated liposarcomas are low grade, nonmetastasizing, malignant neoplasms composed primarily of mature adipose tissue. They are uncommon in the head and neck. CASE: A 24-year-old female presented to the ears, nose and throat clinic for evaluation of a recent, rapidly growing neck mass on the right side. Fine needle aspiration (FNA) biopsy of the mass showed that the smears had fragments of connective tissue with a mixture of mature-appearing fat traversed by bands of fibrous collagen and vessels. Nuclei within the fat and fibrous bands were mildly irregular, hyperchromatic and enlarged, with one or two small nucleoli. Infrequently present but readily identified, lipoblasts were scattered throughout the aspirate smears. A diagnosis of "atypical lipomatous neoplasm" was rendered. Subsequently, the mass was surgically removed. On histologic examination, the tumor was a well-differentiated liposarcoma. CONCLUSION: FNA biopsy of well-differentiated liposarcomas in the head and neck can present difficulties in the classification and diagnosis of this neoplasm.

Adult↗

PubMedDate not supplied

FNAC in the diagnosis of recurrent dermatofibrosarcoma protuberans of the forehead. A case report.

BACKGROUND: Dermatofibrosarcoma protuberans is a rare cutaneous soft tissue tumor of intermediate malignant potential with a characteristic tendency for recurrence. Metastases are unusual. This tumor usually occurs in the trunk and extremities and, infrequently, on the face and scalp. Its cytologic appearance on fine needle aspiration has only been rarely reported. It is characterized by numerous fibroblastlike cells that arrange as single cells or in clusters of spindle cells arrayed in a storiform pattern. CASE: A 42-year-old male presented with a one-year history of an enlarging left forehead mass (lateral brow) that was adjacent to an old surgical scar. Fine needle aspiration revealed a low grade spindle cell neoplasm morphologically identical to a dermatofibrosarcoma protuberans excised 15 years earlier, indicating tumor recurrence. CONCLUSION: Distinguishing dermatofibrosarcoma protuberans from other spindle cell tumors and fibrohistiocytic lesions may pose significant challenges to the pathologist. However, in the appropriate clinical setting and applying strict diagnostic criteria, fine needle aspiration cytology is a reliable tool in establishing the diagnosis of this neoplasm.

Adult↗